Binding of amphiphilic peptides to phospholipid/cholesterol unilamellar vesicles: a model for protein--cholesterol interaction.
In earlier studies, we prepared a docosapeptide, 1, designed with minimum homology as an amphiphilic alpha-helical model of apolipoprotein A-I (apo A-I) and described its lipid-binding characteristics, surface properties, and enzyme-activating ability. Although the affinity of 1 for egg lecithin unilamellar vesicles was comparable with that for the binding of apo A-I, the affinity of 1 for mixed lecithin/cholesterol (4:1 mol/mol) vesicles was less than that of apo A-I. It appeared possible that the 3-hydroxyl group of cholesterol may have a deleterious interaction with the hydrophobic portion of the amphiphilic helix of 1 that is inserted into the vesicles. Examination of the amphiphilic alpha-helical segments of apo A-I suggested that the preferential interaction of apo A-I with the mixed vesicles might be due to the presence of polar arginine residues in the otherwise hydrophobic regions of two of the helices. Therefore, we synthesized a model docosapeptide, 2, corresponding to the sequence of 1 but containing arginine rather than leucine at position 10 in the hydrophobic region of the alpha helix to assess the role of the alcohol function of cholesterol in protein--cholesterol interactions. The results of studies on the binding of 2 to unilamellar vesicles containing lecithin only, lecithin/cholesterol, lecithin/cholesterol hemisuccinate, or lecithin/cholesterol methyl ether were consistent with the postulate that the major role of cholesterol in the binding of proteins to phospholipid surfaces is the creation of free space between the phospholipid head groups that can accommodate the amphiphilic peptide chains at the interface.
D000595:Amino Acid Sequence; D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D002784:Cholesterol; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL; D008081:Liposomes; D009842:Oligopeptides; D010713:Phosphatidylcholines; D011485:Protein Binding
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D008075:Lipoproteins, HDL; D008081:Liposomes; D009842:Oligopeptides; D010713:Phosphatidylcholines; D002784:Cholesterol